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Biomedical subjects

Z Yuan

Publications and source records attributed to Z Yuan.

At least 127 records · Page 7Linked to original sources

The indeterminate gene encodes a zinc finger protein and regulates a leaf-generated signal required for the transition to flowering in maize.

Flowering in plants is a consequence of the transition of the shoot apex from vegetative to reproductive growth in response to environmental and internal signals. The indeterminate1 gene (id1) controls the transition to flowering in maize. We show by cloning the id1 gene that it encodes a protein with zinc finger motifs, suggesting that the id1 gene product functions as a transcriptional regulator of the floral transition. id1 mRNA expression studies and analyses of transposon-induced chimeric plants indicate that id1 acts non-cell-autonomously to regulate the production of a transmissible signal in the leaf that elicits the transformation of the shoot apex to reproductive development. These results provide molecular and genetic data consistent with the florigen hypothesis derived from classical plant physiology studies.

Amino Acid Sequence↗

Purification and physical characterization of cloned human cAMP phosphodiesterases PDE-4D and -4C.

Individual isozymes of family four cyclic-nucleotide phosphodiesterases (PDE-4s) were characterized and compared in order to advance our understanding of how PDE-4s regulate cAMP levels in cells. Full-length and shorter clones containing various functional domains were constructed and overexpressed using a recombinant baculovirus-infected Sf9 insect cell system. One form each of PDE-4C and 4D was purified 125- and 534-fold, respectively, using anion-exchange and affi-gel blue chromatography. The purified material was unaltered in size on SDS-polyacrylamide gels during purification and nearly homogeneous (> 95%) as estimated by both staining and immunoblotting. Approximately 1 mg of PDE-4D (74.7 kDa) and 3.7 mg of PDE-4C (61.4 kDa) could be isolated from a 6-L culture of cells. The physical characteristics of Stokes' radius and sedimentation coefficient for PDE-4 enzymes cloned from each of the four isogenes were determined using size-exclusion chromatography and sedimentation in glycerol gradients. Calculations indicate that both long and short forms can form dimers, although evidence for monomers and higher-order subunit association was seen. Furthermore, the results clearly show that all long and short forms of PDE-4 are highly asymmetric molecules. This work has shown that large amounts of PDE-4 proteins can be purified and characterized physically and enzymatically to yield information that will enable a greater understanding of how PDE-4 enzymes function in cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media.

BACKGROUND: Acute otitis media (AOM) is a common childhood infectious disease. The efficacy of antibiotic dosing regimens is usually assessed by antibiotic plasma pharmacokinetics or middle ear fluid (MEF) concentration at one or two time points. Viral coinfection in AOM reduced antibacterial efficacy of antibiotics. OBJECTIVE: To determine amoxicillin MEF penetration and pharmacokinetics in bacterial and combined bacterial and viral AOM. METHODS: Thirty-four children with AOM were enrolled, and MEF was collected by tympanocentesis for bacterial culture and viral studies. Nasal wash and venous blood were also obtained for viral culture and serologic studies, respectively. Subjects were treated with amoxicillin 40 mg/kg/day orally, divided in equal doses every 8 h. During the second visit (48 to 72 h later) the subjects, with the regular morning amoxicillin dose withheld, were given an oral amoxicillin dose of 25 mg/kg. Thereafter two blood samples and one MEF sample by tympanocentesis were collected from each child at selected times between 0.5 and 4.0 h after dosing for bacterial and viral studies and amoxicillin concentration determination by high performance liquid chromatography. RESULTS: Eleven (37%) children had only bacterial infection, 6 (20%) had viral infection only, 6 (20%) had both bacterial and viral infections and in 7 (23%) neither bacterial nor viral pathogens were recovered. MEF bacterial culture was positive in 23 of 40 ears (57.5%) before treatment with amoxicillin (40 mg/kg/day) and was still positive in 4 of 38 ears (10.5%) after 2 to 3 days of treatment. Amoxicillin plasma concentration reached its peak at 1.0 to 1.5 h after a 25-mg/kg oral dose. The estimated MEF concentration peak occurred 3.0 h after the dose with MEF concentrations ranging from undetectable to 20.6 microg/ml and a mean of approximately 9.5 microg/ml. Geometric mean amoxicillin concentrations were lowest in virus-infected children (2.7 microg/ml), nearly the same in culture-negative samples from children without viral infection (2.9 microg/ml), higher in children with combined bacterial and viral infection (4.1 microg/ml) and highest in children with bacterial-only infection (5.7 microg/ml). CONCLUSIONS: MEF amoxicillin penetration tended to be lower in children with viral infection. The current amoxicillin dosing recommendation of 40 mg/kg/day in three divided dose is inadequate to effectively eradicate resistant Streptococcus pneumoniae, particularly during viral coinfection. A dosing regimen of 75 to 90 mg/kg/day is recommended for AOM.

Acute Disease↗

Hypoglycemic effect of water-soluble polysaccharide from Auricularia auricula-judae Quel. on genetically diabetic KK-Ay mice.

The hypoglycemic effect of water-soluble polysaccharide(FA) from fruiting bodies of Auricularia auricula-judae Quel. was investigated on genetically diabetic mice (KK-Ay) from 10 to 14 weeks of age. Male mice were divided into 3 groups, the control group and FA-fed group having free access to the control diet or FA diet (30 g of FA/kg of diet). The food-restricted group had restricted access to the control diet at the level of the diet consumed by the FA-fed group. Compared with the control group, FA supplementation had a significant effect in lowering plasma glucose, insulin, urinary glucose, and food intake. FA administration also increased the tolerance to intraperitoneal glucose loading and the hepatic glycogen content. In the food-restricted group, the reduced food intake slightly lowered the plasma and urinary glucose levels, but did not improve hyperinsulinemia and glucose tolerance. This study shows that FA had a hypoglycemic effect on KK-Ay mice, and the reduced food consumption was not a major factor which contributed to the hypoglycemic action of FA.

Agaricales↗

An ecological study of the effectiveness of mammography in reducing breast cancer mortality.

OBJECTIVES: The purpose of this study was to determine the relation of screening mammography to breast cancer incidence and case fatality. METHODS: In a sample of White female Medicare beneficiaries hospitalized in 1990-1991, age-adjusted breast cancer incidence and 2-year case fatality rates were estimated and compared with the frequency of mammographic screening from a population-based survey. RESULTS: The average rates for incidence, case fatality, and mammography within 5 years in 29 states were 414/100,000, 18.8%, and 59.2%, respectively. There was a positive state-level correlation between mammography rates and incidence and an inverse correlation between mammography and case fatality. CONCLUSIONS: High screening mammography rates in some states are associated with reduced breast cancer case fatality rates, presumably as a result of diagnosis of earlier stage cancers.

Aged↗

Atrial fibrillation as a risk factor for stroke: a retrospective cohort study of hospitalized Medicare beneficiaries.

OBJECTIVES: This study examined the relationship between atrial fibrillation and (1) stroke and (2) all-cause mortality. METHODS: All eligible Medicare patients older than 65 years of age hospitalized in 1985 were followed up for 4 years. Kaplan-Meier and Cox proportional hazards models were used for assessment of risk of stroke and mortality. RESULTS: A total of 4,282,607 eligible Medicare patients were hospitalized in 1985. The mean age was 76.1 (+/- 7.7) years; 58.7% were female; 7.2% were Black; and 8.4% had a diagnosis of atrial fibrillation. During the follow-up period, 66,063 patients (32.6/1000 person-years) developed nonembolic stroke and 7285 (3.6/1000 person-years) developed embolic stroke. After adjustment for age, race, sex, and comorbid conditions, atrial fibrillation remained a significant risk factor for both nonembolic stroke (relative risk [RR] = 1.56) and embolic stroke (RR = 5.80) and for mortality (RR = 1.31). Approximately 4.5% of nonembolic and 28.7% of embolic strokes among hospitalized Medicare patients aged 65 years and older were attributable to atrial fibrillation. CONCLUSIONS: This study demonstrates that atrial fibrillation is associated with an appreciable increase in the risk of stroke (both embolic and nonembolic) and in the risk of mortality from all causes.

Aged↗

Ameliorating effects of water-soluble polysaccharides from woody ear (Auricularia auricula-judae Quel.) in genetically diabetic KK-Ay mice.

We investigated the ameliorating effects of the three groups of water-soluble polysaccharides, a mixture of crude polysaccharides (FA), acidic polysaccharide fractions (FA-A), and neutral polysaccharide fractions (FA-N), obtained from the hot water extracts of the fruit bodies of Auricularia auricula-judae Quel. In genetically diabetic KK-Ay mice from 6 to 11 weeks of age. Male mice were divided into five dietary groups: 1) control group, given a basal diet; 2) FA group, given an FA diet (15 g FA/kg diet); 3) FA-A group, given an FA-A diet (8 g FA-A/kg diet); 4) low FA-N group, given a low FA-N diet (2 g FA-N/kg diet); and 5) high FA-N group, given a high FA-N diet (8 g FA-N/kg diet). Compared with the control diet, FA supplementation had significant effects in lowering fasting and nonfasting blood glucose, HbA1c, urinary glucose, food intake, and water intake. FA administration also improved glucose tolerance to intraperitoneal glucose loading, but it did not affect the nonfasting insulin level. FA-N supplementation had dose-dependent effects in lowering fasting and nonfasting food glucose, insulin, HbA1c, urinary glucose, food intake, and water intake. However, the glucose tolerance was not ameliorated by either the low or the high FA-N diet. FA-A administration showed no beneficial effects in KK-Ay mice.

Agaricales↗

[Free fatty acids promoting PTP1B expression in rat skeletal muscle and hepatic cells].

OBJECTIVE: To determine whether that free fatty acids (FFAs) impair glucose metabolism is associated with altered insulin signaling system. METHODS: After skeletal muscle and hepatic cells were incubated with palmitate (0.25 mmol/L) or oleate (0.125 mmol/L) for 6, 12 or 24 hours, the protein abundance of SH-PTP2 and PTP1B was assessed by western blot. RESULTS: SH-PTP2 protein levels showed no significant change in both fatty acids treated muscle and hepatic cells at all time points. The PTP1B was significantly elevated in both liver and muscle cells incubated with FFAs at 6, 12 and 24 hours. CONCLUSIONS: FFAs promote the expression of PTP1B in rat skeletal muscle and liver cells, and the elevated PTP1B may mediate the insulin resistance induced by FFAs.

Animals↗

[Study on the analysis of zinc 5-aminosalicylate and related compounds by high performance liquid chromatography].

In this paper, the separation and determination conditions of zinc 5-aminosalicylate (ZASA) and related compounds by high performance liquid chromatography(HPLC) have been studied systematically. The baseline separation was achieved at 20 degrees C on a CLC-ODS column(150 mm x 6.0 mm i.d., 10 microns) within 10 minutes by using 1% (V/V) HAc-MeOH(4:6) as mobile phase at a flow-rate of 1 mL/min. The RSDs of rention time within day and between days were less than 2% and 5% respectively. The injection volume was 20 microL, and relationships between the peak area with 280 nm detection and the analyte concentration were linear within certain ranges. This method was used for determination of ZASA, impurities and thermal decomposition compounds. The results showed that the impurities in the crude ZASA were 5-aminosalicylic acid and salicylic acid. The thermal decomposition compounds in acid medium were 5-aminosalicylic acid, 5-aminophenol and 5-benzeneazosalicylic acid.

Anti-Inflammatory Agents, Non-Steroidal↗

[The role of basic fibroblast growth factor on expression of mineralization of periodontal ligament cell population and clones].

OBJECTIVE: To determine the effect of basic fibroblast growth factor (bFGF) on mineraliztion of PDL cell clone. METHODS: The PDL tissue that derived from three human donors was cultured and cells were cloned. The mineralizing ability were detected with or without bFGF treatment in the presence of dexamethasone. Cloned progenitor populations were assayed for their constitutive capacity to bind CAP and express ALP. RESULTS: The results show that bFGF increases clone mineralization (11%), but not in PDL cell population. The cell clones that mineralized only in the presence of bFGF have higher CAP binding ability and lower ALP expression compared with other mineralized clone cells. CONCLUSION: bFGF enhances mineralizing expression of PDL clone. The clones that mineralized only with bFGF treatment are different cell types from the bFGF-undependent mineralized clones.

Adult↗

Role of protein kinase C in the regulation of pumping activity in bovine mesenteric lymphatic vessels.

We investigated the role of protein kinase C (PKC) in regulating the lymphatic myogenic response. Bovine mesenteric lymphatics were suspended in an organ bath with inflow and outflow ends cannulated. Input was provided from a reservoir filled with Krebs solution. The PKC activator phorbol 12-myristate 13-acetate (PMA) inhibited pumping significantly whether tested at a fixed pressure or as pressures were raised in 2 cm H2O increments (50% inhibition achieved at 4.6 x 10(-8)M. The inactive phorbol ester (4-alpha-PMA) had no effect. The specific PKC inhibitors calphostin (10(-9) to 10(-7)M) or chelerythrine (10(-8) to 10(-6)M) had no significant effect on pumping. However, chelerythrine (10(-6)M) was capable of reversing the inhibitory effects of PMA (5 x 10(-8)M). PKC activation is believed to inhibit nitric oxide (NO) production in some blood vessels, and previous work from our laboratory has demonstrated that NO is important in facilitating pumping activity in bovine lymphatics. We observed that sodium nitroprusside (sNP, 10(-7)M) or L-arginine (10(-4)M), reversed the depressor effects of PMA. These results suggest that PKC may not be involved in regulating the vessel's contractile response to pressure-induced stretch. However, the data with PMA suggest that these ducts contain PKC. PKC activation depresses lymphatic pumping and this effect may be mediated in part, by inhibition of NO.

Alkaloids↗

High-performance liquid chromatographic analysis of amoxicillin in human and chinchilla plasma, middle ear fluid and whole blood.

We extended the application of a sensitive high-performance liquid chromatography assay of amoxicillin developed in this laboratory for human plasma and middle ear fluid (MEF) to other sample matrices including chinchilla plasma or MEF and human and chinchilla whole blood with minor modification and validated the limit of quantitation at 0.25 microg/ml with a 50-microl sample size for human and chinchilla plasmas or MEFs. Amoxicillin and cefadroxil, the internal standard, were extracted from 50 microl of the samples with Bond Elut C18 cartridges. The extract was analyzed on a Keystone MOS Hypersil-1 (C8) column with UV detection at 210 nm. The mobile phase was 6% acetonitrile in 5 mM phosphate buffer, pH 6.5 and 5 mM tetrabutylammonium. The within-day coefficients of variation were 2.7-9.9 (n=4) and 1.7-7.2% (n=3) for chinchilla plasma and MEF samples, respectively; 2.8-8.1% (n=3) and 2.9-4.7% (n=3) for human and chinchilla whole blood, respectively. An alternative mobile phase composition for chinchilla plasma and MEF samples reduced the analysis time significantly.

Amoxicillin↗

A high-density screening format for encoded combinatorial libraries: assay miniaturization and its application to enzymatic reactions.

A novel, miniaturized high-throughput screening format is described for assay of combinatorial libraries generated on beads. This approach, which is ideally suited to encoded libraries synthesized on beads, utilizes the photolytic cleavage of individual compounds into a high-density well array (>6500 wells within a standard 96-well microtiter plate footprint) with well volumes as low as 0.37 microl. As a model study, an encoded dipeptide library (324 members) acylated with isobutyl succinate was assayed using this format to search for potential inhibitors of matrilysin, a member of the matrix metalloproteinase superfamily. In situ release of compounds from solid support was accomplished by photochemical cleavage after beads and enzyme were distributed to the wells. After the addition of a fluorogenic substrate to the array, the extent of enzyme inhibition and identification of active compounds was quantitated by imaging of the fluorescence emission upon uv irradiation. The structure-activity relationship data generated from the identified inhibitors in this study corroborate previous findings, thus validating the utility of this approach as a means of high-throughput screening of bead-based libraries.

Acylation↗

Alendronate prevents cyclosporin A-induced osteopenia in the rat.

Post-transplantation bone disease is an increasingly recognized clinical entity whose etiology is multifactorial. The immunosuppressant agent cyclosporine-A (CsA) has repeatedly been shown experimentally to induce a high-turnover osteopenic state. Alendronate (Alen.) is a new generation bisphosphonate having far greater antiresorptive potency than previous bisphosphonates. It inhibits osteoclast resorption in vitro and in vivo without adversely affecting bone mineralization. This study was designed to investigate whether alendronate could prevent CsA-induced osteopenia in the rat. Forty-eight 8-month-old male Sprague Dawley rats were randomized into four groups to receive the following for 28 days: (1) CsA vehicle (veh.) p.o. daily and alendronate vehicle subcutaneously (s.c.) twice/week, (2) CsA 15 mg/kg p.o. daily and Alen. veh. s.c. twice/week, (3) Alen. 70 micrograms/kg s.c. twice/ week and CsA veh. p.o. daily, and (4) CsA 15 mg/kg p.o. daily and Alen. 70 micrograms/kg s.c. twice/week. Rats were weighed and bled and serum was assayed serially for calcium, PTH, 1,25(OH)2vit.D, and osteocalcin. Tibiae were removed following sacrifice on day 28, after double demeclocycline and calcein labeling, for histomorphometric analysis. Treated groups were compared to the vehicle-treated control. We confirmed previous findings that CsA produces elevated 1,25(OH)2 vitamin D and serum osteocalcin levels. Alendronate treatment by itself decreased osteocalcin by day 28 and resulted in a marginal decrease in serum total calcium on day 14. The histomorphometry findings reconfirmed that the administration of CsA induces a state of high-turnover osteopenia. Alendronate prevented CsA's adverse effects, particularly in maintaining trabecular bone volume, presumably by decreasing bone remodeling. Alendronate would seem to hold therapeutic promise in post-transplantation bone disease.

Administration, Oral↗

Lack of gender and racial differences in surgery and mortality in hospitalized Medicare beneficiaries with bleeding peptic ulcer.

OBJECTIVE: Determine the relation of race and gender to outcome from bleeding peptic ulcer. DESIGN: Retrospective cohort study. SETTING: All acute care hospitals in the United States. PATIENTS: A 100% sample of hospitalized Medicare beneficiaries older than 64 years (n = 82,868) with a primary discharge diagnosis of peptic ulcer with hemorrhage. MEASUREMENTS AND MAIN RESULTS: Surgical treatment was performed in 6.9% of patients, 30-day mortality was 8.5%, and average length of stay was 9.4 days. Surgery was somewhat more common in men than women (7.3% vs 6.5%, p < .001), and in whites than African Americans (6.9% vs 6.3%, p < .001), but neither race nor gender was associated with surgery in multivariable analysis adjusting for potentially confounding factors. Mortality rates were similar in African Americans and whites (8.5%), and somewhat higher in men than women (10.7% vs 9.3%, p < .001). In multivariable analysis, there was no difference in mortality across gender and racial groups. Although unadjusted and adjusted lengths of stay were longer for African Americans and shorter for men, the differences were modest (i.e., 16% increase and 6% decrease in multivariable analysis, respectively, p < .0001). CONCLUSIONS: In this national sample, there is no significant gender or racial difference in therapy and outcome for patients with hemorrhagic peptic ulcer. The findings raise the possibility that studies that have shown race and gender differences in management of coronary artery disease and cancer may not be generalizable to other common diagnoses.

Black or African American↗

The role of testosterone in cyclosporine-induced osteopenia.

Our laboratory has demonstrated that the immunosuppressants Cyclosporin A (CsA) and tacrolimus (FK506), in vivo in the rat, produce a high-turnover osteopenia. CsA is known to decrease serum testosterone (Test) levels both in the rat and in human transplant patients. Less is known of FK506's effect on androgens. CsA-induced hypogonadism may contribute to the aforementioned bone loss because hypogonadism itself is a risk factor for osteoporosis and fracture. The aim of this study was to assess serum androgen levels following CsA and FK506 therapy and to see wether Test replacement therapy, in the form of 28-day controlled release subcutaneous pellet implants, could prevent CsA-induced osteopenia. Two experiments were conducted. In experiment I, four groups of 6-month-old male Sprague-Dawley rats received the following: (A) CsA vehicle and placebo pellet, (B) Test 15 mg pellet and CsA vehicle, (C) CsA 10 mg/kg and placebo pellet, (D) Test 15 mg pellet and CsA 10 mg/kg. In experiment II, two groups of rats received (E) FK506 vehicle and (F) FK506 4 mg/kg. CsA, FK506, and vehicles were given for 28 days by daily oral gavage. The rats were weighted and bled on days 0, 14, and 28. All rats received double fluorescent labeling, and on day 28 the tibiae were removed for histomorphometry. Whole blood was assayed for CsA and FK506 levels. Serum was assayed for total and free Test as well as for osteocalcin (BGP), blood urea nitrogen (BUN), creatinine, and calcium. Whole blood monoclonal CsA levels measured by fluorescent immunoassay were in the therapeutic range, while a drug concentration profile showed good absorption of FK506. Those rats receiving Test and FK506 lost weight, while those receiving CsA remained constant. BUN was only marginally elevated in the CsA-treated groups on day 28 (p < 0.05), while creatinine was unchanged. On day 28, total and free Test was significantly reduced in the CsA-treated rats versus control (p < 0.05), while Test replacement therapy maintained total Test levels above vehicle (p < 0.01) and free Test levels similar to vehicle on day 28. FK506 did not lower total or free Test levels. BGP levels were significantly increased in the CsA (p < 0.01) and FK506 (p < 0.001) groups on day 28. BGP in the groups receiving Test alone and in combination with CsA remained similar to vehicle. Histomorphometry confirmed CsA- and FK506-induced high-turnover osteopenia. The Test alone group marignally increased bone formation. Test replacement failed to prevent the CsA-induced bone loss. In conclusion, immunosuppressive doses of CsA, but not FK506, lowers serum total and free Test. Hypoandrogenemia does not seem to be a major factor in CsA-induced osteopenia because bone loss occurs despite Test replacement.

Animals↗

Mortality rates, hospital length of stay, and the cost of treating subarachnoid hemorrhage in older patients: institutional and geographical differences.

The risk of disability and death and the cost of medical care are particularly high for patients with aneurysmal subarachnoid hemorrhage (SAH) who are 65 years of age or older. A retrospective analysis of 47,408 Medicare patients treated over an 8-year period was performed to determine whether a relationship exists between the mortality rate and surgical volume for older patients with SAH. The mortality rate, length of stay in the hospital, and cost of treatment for patients with SAH in California and New York state were also compared. The mortality rate was 14.3% for patients with SAH who were 65 years old or older and who were treated surgically in hospitals in which an average of five or more craniotomies were performed per year; in hospitals averaging between one and five craniotomies annually the mortality rate was 18.4%; and in those averaging less than one such operation per year the rate was 20.5% (trend p = 0.01). There was no difference in the mortality rate for patients in California versus the rate for those in New York. Surgically and medically treated patients, respectively, left the hospital an average of 6.7 and 5.1 days sooner in California than in New York. The unadjusted average reimbursement from Medicare to hospitals for surgically treated patients averaged $1468 more in New York than in California (p < 0.0001), but was equivalent for medically treated patients in the two states. The mortality rate in older patients who are treated surgically for SAH may be inversely correlated with the annual number of craniotomies performed for SAH in patients 65 years of age or older at a given institution. Hospital stays for patients with SAH are significantly shorter in California than in New York.

Aged↗

[A 20-year experience in surgical management of acute necrotizing pancreatitis].

From 1974 to 1994, 243 patients with acute necrotizing pancreatitis (ANP) proved by operation or CT scanning system were treated. The overall survival rate was 70.4%. In 1974-1987, the resection of necrosis was radical and as early as possible, and the main type of operation was subtotal pancreatectomy. The survival rate in this period was 61.3% (49/80). In 1988-1991, the treatment was changed into "individualization" i.e. for sterile pancreatic necrosis, conservative treatment was setected while infected pancreatic necrosis, necrosectomy was performed early. In this period, the survival rate of conservative treatment was 85.7% (6/7) and that of operative treatment 67.1%. The overall survival rate in was 68.5% (63/92). In 1991-1994, we insisted on late operation for the patients with necrosis and comprehensive management for all the patients with ANP. The survival rate of conservative treatment in this period was 100% (11/11) and that of operative treatment 80% (48/60). The overall survival rate was 83.1% (59/71). We conclude that comprehensive management combined with late operation for the patients with necrosis infected is a better strategy for the treatment of ANP.

Adolescent↗